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Lipid bilayer modification alters the gating properties and pharmacological sensitivity of voltage-gated sodium channel

ZHU Yan, WU Bin, FENG Yi-Ju, TAO Jie, JI Yong-Hua

1Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, China； 2Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China； 3Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China

Abstract

Voltage-gated sodium channels (VGSCs) are widely distributed in most cells and tissues, performing many physiological functions. As one kind of membrane proteins in the lipid bilayer, whether lipid composition plays a role in the gating and pharmacological sensitivity of VGSCs still remains unknown. Through the application of sphingomyelinase D (SMaseD), the gating and pharmacological sensitivity of the endogenous VGSCs in neuroblastoma ND7-23 cell line to BmK I and BmK AS, two sodium channel-specific modulators from the venom of Buthus martensi Karsch (BmK), were assessed before and after lipid modification. The results showed that, in ND7-23 cells, SMaseD did not change the gating properties of VGSCs. However, SMaseD application altered the slope factor of activation with the treatment of 30 nmol/L BmK I, but caused no significant effects at 100 and 500 nmol/L BmK I. With low concentration of BmK I (30 and 100 nmol/L) treatment, the application of SMaseD exerted hyperpolarizing effects on both slow-inactivation and steady-state inactivation, and increased the recovery time constant, whereas total inactivation and recovery remained unaltered at 500 nmol/L BmK I. Meanwhile, SMaseD modulation hyperpolarized the voltage dependence of slow-inactivation at 0.1 nmol/L BmK AS and altered the slope factor of slow-inactivation at 10 nmol/L BmK AS, whereas other parameters remained unchanged. These results indicated a possibility that the lipid bilayer would disturb the pharmacological sensitivity of VGSCs for the first time, which might open a new way of developing new drugs for treating sodium channelopathies.

Key words: sphingomyelinase D; sodium channels; ND7-23 cell line; BmK I; BmK AS

Received: 2015-03-17　　Accepted: 2015-05-19

Corresponding author: 陶杰,吉永华　　E-mail: yhji@staff.shu.edu.cn, jietao_putuo@foxmail.com

Citing This Article：

ZHU Yan, WU Bin, FENG Yi-Ju, TAO Jie, JI Yong-Hua. Lipid bilayer modification alters the gating properties and pharmacological sensitivity of voltage-gated sodium channel. Acta Physiol Sin 2015; 67 (3): 271-282 (in Chinese with English abstract).